| 摘要: |
| 目的:为了解决患者来源类器官模型是否可以充当患者的疾病模型替代物,以及他们在多大的分子程度上替代原始患者肿瘤,使用单细胞转录组测序分析来深入了解临床前模型的性质,促进胰腺癌患者的精准医疗。方法:收集来自胰腺癌公开的相关单细胞转录组测序数据集以及临床数据,进行质控、降维、聚类和细胞注释后,使用差异基因表达分析、GO、KEGG富集分析、细胞通讯分析和生存预后分析,探索免疫细胞在胰腺癌原发性肿瘤和患者来源类器官上构成和分布,筛选出显著差异表达基因,以及免疫细胞互作关系等。结果:我们成功识别了22个细胞群,并进一步将其分成11类不同的细胞类型,我们对免疫细胞之间的互作关系做了初步研究,分析得到中性粒细胞以及TGF-β信号通路在各个方面占有主导地位,生存分析得到FFAR2、RASGEF1C在胰腺癌中增加可以抑制肿瘤生长。结论:原发性肿瘤和类器官在免疫细胞类型比例分布出现异质性,在细胞通讯中,中性粒细胞在TGF-β信号通路中有着活跃的细胞间相互作用,为胰腺癌的免疫治疗提供新的治疗靶点,为类器官的发展奠定新的理论基础。 |
| 关键词: 单细胞转录组测序 胰腺癌 原发性肿瘤 患者来源类器官 |
| DOI： |
| 分类号: |
| 基金项目:] 广西壮族自治区卫生健康委员会自筹经费课题(Z20211048)。 |
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| Advances in single-cell sequencing to explore patient-derived organoids in pancreatic adenocarcinoma disease |
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xuyingcui1,2,3,2,4
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1.Guangxi Zhuang Autonomous Region People&2.#39;3.&4.s Hospital
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| Abstract: |
| Objective: To address whether patient-derived organoid (PDO) models can act as disease model substitutes for patients, and what is the maximum molecular extent to which they replace the original patient"s tumor, single-cell RNA sequencing(scRNA-seq) analyses were used to gain insights into the nature of the preclinical models and to facilitate precision medicine for pancreatic cancer patients. Methods: Relevant scRNA-seq datasets from publicly available pancreatic cancer and clinical data were collected,after quality control, downscaling, clustering, and cellular annotation, differential gene expression analyses, GO, KEGG enrichment analyses, cellular communication analyses, and survival prognostic analyses were used to explore the composition and distribution of immune cells on primary tumors and PDO, to screen for significantly differentially expressed genes, as well as immune cell interactions, etc. Results: We successfully identified 22 cell populations and further classified them into 11 different cell types, we did a preliminary study on the interactions between immune cells, and the analysis yielded that neutrophils as well as the TGF-β signaling pathway dominated in all aspects, and the survival analysis yielded that the increase of FFAR2, and RASGEF1C in pancreatic cancer could inhibit tumor growth. Conclusion: Primary tumors and organoids appear heterogeneous in the proportionate distribution of immune cell types, and neutrophils have an active intercellular interaction in the TGF-β signaling pathway in cellular communication, which provides a new therapeutic target for the immunotherapy of pancreatic cancer, and lays a new theoretical foundation for the development of organoids. |
| Key words: Single-cell sequencing Pancreatic adenocarcinoma Primary tumor Patient-derived organoid |
